Mechanistic and Physiological Implications of the Interplay among Iron鈥揝ulfur Clusters in [FeFe]-Hydrogenases. A QM/MM Perspective

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• 作者：Claudio Greco ; Maurizio Bruschi ; Piercarlo Fantucci ; Ulf Ryde ; Luca De Gioia
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：November 23, 2011
• 年：2011
• 卷：133
• 期：46
• 页码：18742-18749
• 全文大小：1033K
• 年卷期：v.133,no.46(November 23, 2011)
• ISSN：1520-5126

文摘

Key stereoelectronic properties of Desulfovibrio desulfuricans [FeFe]-hydrogenase (DdH) were investigated by quantum mechanical description of its complete inorganic core, which includes a Fe₆S₆ active site (the H-cluster), as well as two ancillary Fe₄S₄ assemblies (the F and F鈥?clusters). The partially oxidized, active-ready form of DdH is able to efficiently bind dihydrogen, thus starting H₂ oxidation catalysis. The calculations allow us to unambiguously assign a mixed Fe(II)Fe(I) state to the catalytic core of the active-ready enzyme and show that H₂ uptake exerts subtle, yet crucial influences on the redox properties of DdH. In fact, H₂ binding can promote electron transfer from the H-cluster to the solvent-exposed F鈥?cluster, thanks to a 50% decrease of the energy gap between the HOMO (that is localized on the H-cluster) and the LUMO (which is centered on the F鈥?cluster). Our results also indicate that the binding of the redox partners of DdH in proximity of its F鈥?cluster can trigger one-electron oxidation of the H₂-bound enzyme, a process that is expected to have an important role in H₂ activation. Our findings are analyzed not only from a mechanistic perspective, but also in consideration of the physiological role of DdH. In fact, this enzyme is known to be able to catalyze both the oxidation and the evolution of H₂, depending on the cellular metabolic requirements. Hints for the design of targeted mutations that could lead to the enhancement of the oxidizing properties of DdH are proposed and discussed.